rs2453839

chr7-45913974-T-Cchr7-45913974-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000598.5(IGFBP3):c.*16-140A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 152,086 control chromosomes in the GnomAD database, including 5,395 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.25 (5395 hom., cov: 33)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: IGFBP3 NM_000598.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61

Genes affected

IGFBP3 (HGNC:5472): (insulin like growth factor binding protein 3) This gene is a member of the insulin-like growth factor binding protein (IGFBP) family and encodes a protein with an IGFBP domain and a thyroglobulin type-I domain. The protein forms a ternary complex with insulin-like growth factor acid-labile subunit (IGFALS) and either insulin-like growth factor (IGF) I or II. In this form, it circulates in the plasma, prolonging the half-life of IGFs and altering their interaction with cell surface receptors. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGFBP3	NM_000598.5	c.*16-140A>G		intron_variant		ENST00000613132.5
IGFBP3	NM_001013398.2	c.*16-140A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGFBP3	ENST00000613132.5	c.*16-140A>G		intron_variant		5	NM_000598.5	P4
IGFBP3	ENST00000381083.9	c.*16-140A>G		intron_variant		5		A1
IGFBP3	ENST00000381086.9	c.*16-140A>G		intron_variant		2
IGFBP3	ENST00000460209.1	n.522-140A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38098 AN: 151966 Hom.: 5383 Cov.: 33

Gnomad AFR AF: 0.397

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.172

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.229

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.251 AC: 38135 AN: 152084 Hom.: 5395 Cov.: 33 AF XY: 0.248 AC XY: 18419 AN XY: 74356

Gnomad4 AFR AF: 0.397

Gnomad4 AMR AF: 0.163

Gnomad4 ASJ AF: 0.239

Gnomad4 EAS AF: 0.198

Gnomad4 SAS AF: 0.181

Gnomad4 FIN AF: 0.196

Gnomad4 NFE AF: 0.202

Gnomad4 OTH AF: 0.226

Alfa AF: 0.198 Hom.: 4144

Bravo AF: 0.255

Asia WGS AF: 0.196 AC: 678 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.26
Dann	Benign	0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2453839; hg19: chr7-45953573;